title: Defective mismatch repair and benefit from bevacizumab for colon cancer: findings from NSABP C-08.
abstract: National Surgical Adjuvant Breast and Bowel Project protocol C-08 tested the worth of adding 1 year of bevacizumab to oxaliplatin-based standard adjuvant chemotherapy regimen in the treatment of stage II/III colon cancer. Although the overall result was negative, the possibility that a molecularly defined subset could benefit from bevacizumab cannot be ruled out. We performed post hoc Cox regression analyses to test for marker-by-treatment interactions for standard pathological features and survival analyses using the Kaplan-Meier method. All statistical tests were two-sided and considered statistically significant at the .05 level. Patients diagnosed with mismatch repair defective (dMMR) tumors derived statistically significant survival benefit from the addition of bevacizumab (hazard ratio [HR] = 0.52; 95% confidence interval [CI] = 0.29 to 0.94; P = .02) in contrast with no benefit in patients diagnosed with mismatch repair proficient tumors (HR = 1.03; 95% CI = 0.84 to 1.27; p = .78; P(interaction)= .04). Although a post hoc finding, this data suggests that a molecularly defined subset of colon cancer patients may derive clinical benefit from antiangiogenesis agents and underscores the need for independent validation in other clinical trials.
authors.affiliation: National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA 15212, USA.
authors.forename: Kay
authors.initials: K
authors.lastname: Pogue-Geile
authors.forename: Greg
authors.initials: G
authors.lastname: Yothers
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Taniyama
authors.forename: Noriko
authors.initials: N
authors.lastname: Tanaka
authors.forename: Patrick
authors.initials: P
authors.lastname: Gavin
authors.forename: Linda
authors.initials: L
authors.lastname: Colangelo
authors.forename: Nicole
authors.initials: N
authors.lastname: Blackmon
authors.forename: Corey
authors.initials: C
authors.lastname: Lipchik
authors.forename: Seong Rim
authors.initials: SR
authors.lastname: Kim
authors.forename: Saima
authors.initials: S
authors.lastname: Sharif
authors.forename: Carmen
authors.initials: C
authors.lastname: Allegra
authors.forename: Nicholas
authors.initials: N
authors.lastname: Petrelli
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Connell
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
authors.forename: Soonmyung
authors.initials: S
authors.lastname: Paik
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D053843:DNA Mismatch Repair / Q000187:drug effects*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D017211:Treatment Failure; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077150:Oxaliplatin; D000068258:Bevacizumab; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf